The modulation of fluorouracil with leucovorin in metastatic colorectal carcinoma: a prospective randomized phase III trial. Gastrointestinal Tumor Study Group.

• DOI: 10.1200/jco.1989.7.10.1419
• Publication Date: 2017-02-23T18:04:11Z
• Authors: N Petrelli; H O Douglass; L Herrera; D Russell; D M Stablein; H W Bruckner; R J Mayer; R Schinella; M D Green; F M Muggia
• Keywords: Male; Clinical Trials as Topic; Lung Neoplasms; Liver Neoplasms; Leucovorin; Middle Aged; Drug Administration Schedule; 3. Good health; Random Allocation; 03 medical and health sciences; 0302 clinical medicine; Humans; Drug Interactions; Female; Fluorouracil; Prospective Studies; Neoplasm Recurrence, Local; Colorectal Neoplasms; Aged

A total of 343 patients with previously untreated metastatic measurable colorectal carcinoma were studied to evaluate the impact on toxicity, response, and survival of leucovorin-modulated fluorouracil (5-FU). A maximally tolerated intravenous bolus loading course regimen of 5-FU alone (500 mg/m2 x 5 days every 4 weeks with 25 mg/m2 escalation) was compared with a high-dose leucovorin regimen (600 mg/m2 of 5-FU with 500 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest) and with a similar low-dose leucovorin regimen (600 mg/m2 of 5-FU with 25 mg/m2 of leucovorin weekly for 6 weeks with a 2-week rest). The dose-limiting toxicity for the two 5-FU and leucovorin regimens was gastrointestinal, specifically diarrhea; severe diarrhea was seen frequently, and treatment-related toxicity was implicated in the demise of 11 of the patients (5%). Significant improvements in response rates were observed with a response rate of 33 of 109 (30.3%) on the high-dose leucovorin regimen (P less than .01 v control); 13 of 107 (12.1%) on the 5-FU control; and 21 of 112 (18.8%) on the low-dose leucovorin regimen. A trend toward longer survival in the 5-FU plus high-dose leucovorin regimen was observed. In this study, leucovorin was shown to significantly enhance the therapeutic effect of 5-FU in metastatic colorectal carcinoma.